Multicolor Cocktail for Breast Cancer Multiplex Phenotype Targeting and Diagnosis Using Bioorthogonal Surface-Enhanced Raman Scattering Nanoprobes
Multicolor Cocktail for Breast Cancer Multiplex Phenotype Targeting and Diagnosis Using Bioorthogonal Surface-Enhanced Raman Scattering Nanoprobes
复制标题
使用生物正交表面增强拉曼散射纳米探针进行乳腺癌多重表型靶向和诊断的多色混合物
DOI：
10.1021/acs.analchem.9b01382
复制
发表时间：
2019-09-03
影响因子：
7.4
通讯作者：
Tang, Xinjing
中科院分区：
文献类型：
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作者：
Wang, Jing;Liang, Duanwei;Tang, Xinjing
癌症的早期精确诊断对于实现毒性作用最小的更有效的治疗干预至关重要。在治疗过程中，癌症表型也可能在患者之间和个体内发生很大变化。肿瘤细胞上表达的特异性生物标志物的鉴定和表征对于诊断和治疗具有很高的需求，但它们仍然是一个挑战。在此，我们设计了三种新的生物正交表面增强拉曼散射（Sers）纳米探针，并成功地将它们的混合物应用于MDA-MB-231和MCF-7乳腺癌多重表型检测。含有二炔基、叠氮基或氰基基团的拉曼报告分子的Sers纳米探针在生物拉曼沉默区分别在2205、2120和2230 cm（-1）处表现出明显的拉曼位移峰。三个靶配体，包括寡核苷酸适配体（AS 1411），精氨酸-甘氨酸-天冬氨酸（RGD）肽，和归巢细胞粘附分子抗体（抗CD 44），分别缀合到纳米探针的主动识别能力。纳米探针的混合物表现出最小的细胞毒性和同时MDA-MB-231和MCF-7细胞的多重表型成像。通过电感耦合等离子体质谱（ICPMS）定量测量细胞摄取证实，MDA-MB-231细胞具有比MCF-7细胞高得多的CD 44受体表达水平。对于体内Sers检测，在微肿瘤中清晰观察到2120、2205和2230 cm（-1）的拉曼位移峰，代表存在核仁素、整合素α（v）β（3）和CD 44报告基因三种特异性生物标志物，可用于早期癌症表型鉴定。生物分布结果表明，靶向配体修饰的纳米探针在肿瘤中表现出比那些没有靶向配体的纳米探针更多的蓄积。生物正交Sers纳米探针的混合物为早期癌症多重表型靶向和体内诊断提供了一种有吸引力和有洞察力的策略，该策略是非侵入性的，并且具有低串扰，独特的光谱分子特征，高灵敏度和可忽略的背景干扰。
Early precise diagnosis of cancers is crucial to realize more effective therapeutic interventions with minimal toxic effects. Cancer phenotypes may also alter greatly among patients and within individuals over the therapeutic process. The identification and characterization of specific biomarkers expressed on tumor cells are in high demand for diagnosis and treatment, but they are still a challenge. Herein, we designed three new bioorthogonal surface-enhanced Raman scattering (SERS) nanoprobes and successfully applied the cocktail of them for MDA-MB-231 and MCF-7 breast cancer multiplex phenotype detection. The SERS nanoprobes containing Raman reporters with diynl, azide, or cyano moieties demonstrated apparent Raman shift peaks in 2205, 2120, and 2230 cm(-1), respectively, in the biologically Raman-silent region. Three target ligands, including oligonucleotide aptamer (AS1411), arginine-glycine-aspatic acid (RGD) peptide, and homing cell adhesion molecule antibody (anti-CD44), were separately conjugated to the nanoprobes for active recognition capability. The cocktail of the nanoprobes manifested minimal cytotoxicity and simultaneously multiplex phenotype imaging of MDA-MB-231 and MCF-7 cells. Quantitative measurement of cellular uptake by inductively coupled plasma mass spectrometry (ICPMS) verified that MDA-MB-231 cells harbored a much higher expression level of CD44 receptor than MCF-7 cells. For in vivo SERS detection, Raman shift peaks of 2120, 2205, and 2230 cm(-1) in the micro-tumor were clearly observed, representing the existence of three specific biomarkers of nucleolin, integrin alpha(v)beta(3), and CD44 reporter, which could be used for early cancer phenotype identification. The biodistribution results indicated that target ligand modified nanoprobes exhibited much more accumulation in tumors than those nanoprobes without target ligands. The multicolor cocktail of bioorthogonal SERS nanoprobes offers an attractive and insightful strategy for early cancer multiplex phenotype targeting and diagnosis in vivo that is noninvasive and has low cross-talk, unique spectral-molecular signature, high sensitivity, and negligible background interference.